A group of experimental systems which allow the determination of quantitative end points in normal tissue and tumor in the mouse will be used to search for methods which yield improved therapeutic ratios in experimental radiation therapy. Quantitative measurements of normal tissue damage to be applied include pulmonary lethality, esophageal lethality, renal lethality, whole brain lethality, gut clone assay, skin reaction grade assay and mouse bone marrow CFU assay. Tumor end points to be applied include the use of the EMT6 mouse mammary sarcoma in vivo as a solid tumor in the leg, as a solid tumor in the flank and as intravenously transplanted microcolonies in the lung. Using these systems, which have been extensively employed and to a certain extent developed in our laboratory, the damage to normal tissue vs. tumor will be determined and combinations or individual regimes yielding improved tumor kill for a given normal tissue damage determined. Methods of enhancing tumor damage vs. normal tissue damage to be explored include the effect of multiple fractionation of the radiation dose delivery, the effect of alterations in radiation dose rate, the effect of anti-cancer chemotherapeutic agents, the relative effectiveness of particles including Californium 252 neutrons, 15 MeV neutrons and heavy nuclei, and finally the effect of heat. Preliminary work suggests that hyperfractionation and decreased dose rates, certain chemotherapeutic agents, heavy particles and heat will yield improvement of the therapeutic ratio when normal tissue damage is compared to tumor effects.